Trastuzumab-deruxtecan in HER2-low metastatic/unresectable breast cancer: Real life data in two Parisian centers.
Authors: Claire Bieth, Marc Antoine Benderra, Herve Foka Tichoue, Samy Houari, Lamia Hassani, Djamel Ghebriou, Lauren Seknazi, Xavier Barthere, Coralie Prebet, Louise De Forceville, Jean-Pierre Lotz, Joseph Gligorov, Mathieu Jamelot
Journal: Journal of Clinical Oncology (2023)

e13130 Background: Trastuzumab-deruxtecan (TDXT) is an antibody-drug conjugate which has been approved for HER2-positive metastatic breast cancer (BC) treatment. DESTINY-Breast04 phase III clinical trial published in July 2022, TDXD was also shown to increase progression-free and overall survival in patients with HER2-low score metastatic/unresectable BC previously treated by 1 or 2 lines of chemotherapy, regardless of their hormone-receptor (HR) status. TDXD therefore has become a new therapeutic option in this population and has received an early access authorization in November 2022 in France. We report here our first experiences with TDXD in HER2-low patients to discuss some real-life data in this population. Methods: This retrospective descriptive study reports efficacy and safety data of TDXD use in pre-treated metastatic/advanced HER2-low (IHC + or IHC ++/ISH-) BC. Data from the medical records of all HER-2 low BC patients treated with TDXD (5.4 mg/kg, one intravenous injection every 21 days) until December 31, 2022 at Tenon and Pitié-Salpêtrière Hospitals were collected and analyzed. Efficacy was evaluated with PET-scanner comparison. Toxicity was graded using CTCAE 5.0 classification. End-point date for follow-up was February 09th, 2023. Results: We included a total of 22 patients (only women). They had already received several chemotherapy regimens (median 4 range 1-10), 50% had received radiotherapy and 22.7% underwent surgery. 18 (81%) were HR+ whereas 4 had triple negative (TN) cancer. Most commons metastatic sites were bones (73%), lymph nodes (68%) and liver (50%). At TDXD start, median age was 57.9 years. 82% patients had a ECOG score 0-1 and 18% ECOG 2. Median time between initial diagnosis and TDXD start was 77 months (range: 21-240) and from first chemotherapy in metastatic situation and TDXD start was 31 months (range: 3-89). The median duration of TDXD treatment was 5.9 months in HR+ patients and 5.7 months in TN patients. At the 3-month evaluation, 61.1% HR+ patients had a treatment response (50% partial and 11.1% complete), 27.8% a stabilization and 11.1% a progression. The longest treatment follow-up was 12.6 months. Among the 4 TN patients, there were 2 cases of partial response, 1 case of stabilization and one progression at the 3-month evaluation. The longest treatment response was 15.8 months. A total of 7 cancer-related deaths have occurred (6 RH+ and 1 RH-). Out of 22 patients, 86% experienced ≥ 1 adverse effect (AE). They were mainly grade I or II asthenia (63% patients) and nausea (58%). 2 cases of grade III effects (anemia and hepatic cytolysis) were reported. Finally, 3 cases of iatrogenic interstitial lung disease have been observed, one of them being a grade V toxicity. Conclusions: First cases of TDXD use in HER2-low BC patients in 2 French hospitals show promising results with a 54.5% response rate at 3 months. TDXD is globally well tolerated with 13.6% of grade ≥ 3 AE reported.